Methods are known whereby an organism is treated with mutagens such as base analogues (for example 5-bromouracil and 2-aminopurine), substances that chemically modify bases (for example hydroxylamine) or intercalating agents (for example acridines).
This known method requires the addition of chemicals which are hazardous for both the technician handling them and, if not properly disposed of, to the environment. In addition, the modifications are not directed. That is, all the DNA of the organism is mutated and thus an organism with the desired trait will be selected carrying also many other mutations, which mutations may decrease its suitability for the intended use.
It is known that defective DNA polymerase results in an increase in mutations and may result in a desired mutated organism, but replication with defective DNA polymerase does not result in directed mutations. Cairns et al. (1988) describe the phenomenon of adaptive or selection-induced mutation, but this reference does not suggest the method of the present invention.